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December 15, 2010

When a new disease emerges or a familiar one becomes a more significant health threat than it has been in the past, scientists, physicians and public health workers recognize the need for a new way to prevent the disease. Once scientists have identified the organism or toxin that causes the illness, they pursue a number of approaches to develop a vaccine.

Vaccine development has its early roots in the work of Edward Jenner, who discovered how to protect people from smallpox, and Louis Pasteur, who developed a vaccine to protect from rabies. Those pioneering efforts subsequently led to vaccines for diseases that had once claimed millions of lives worldwide.

The purpose of a vaccine is to bring about active immunity by provoking a response from a person's immune system—marshaling B and T cells to swing into action—and creating a memory within the immune system so that exposure to the active disease agent will stimulate an already primed immune system to fight the disease. Some vaccines are combinations that protect against several diseases. Most of us are familiar with the DTP (diphtheria, tetanus, pertussis) and MMR (measles, mumps, rubella) vaccines that children in the United States receive. Scientists extensively test these combination vaccines to make sure that none of the antigens detracts from the immune priming effect of the others. Thus the vaccines can provide triple protection, the recipients are spared extra needle sticks, and the public health costs are reduced.

Based on the biological and chemical characteristics of the disease-causing agent and on what type of immunity is desired, researchers begin to develop one of the following types of vaccines. Vaccines can be produced from 1) inactivated (killed), 2) live, attenuated (weakened), or 3) synthetic (laboratory-made) microbial materials.

Traditional Vaccines

Inactivated Vaccines

Inactivated vaccines are produced by killing the disease-causing microorganism with chemicals or heat. Such vaccines are stable and safe; they cannot revert to the virulent (disease-causing) form. They often do not require refrigeration, a quality that makes them accessible to the people of many developing countries, as well as practical for vaccinating people who are highly mobile, such as members of the armed forces. However, most inactivated vaccines stimulate a relatively weak immune response and must be given more than once. A vaccine that requires several doses (boosters) has a limited usefulness, especially in areas where people have less access to regular health care. The flu shot is an inactivated vaccine, as are the vaccines for cholera, plague, and hepatitis A.

Live, Attenuated Vaccines

To make a live, attenuated vaccine, the disease-causing organism is grown under special laboratory conditions that cause it to lose its virulence, or disease-causing properties. Although live vaccines require special handling and storage in order to maintain their potency, they produce both antibody-mediated and cell-mediated immunity and generally require only one boost, or additional dose. Most live vaccines are injected; some, however, such as the polio vaccine, are given orally. In addition, intranasal vaccines, administered in the nose, show promise in preventing flu.

While there are advantages to live vaccines, there is one caution. It is the nature of living things to change, to mutate, and the organisms used in live vaccines are no different. There is a remote possibility that the organism may revert to a virulent form and cause disease. It is for this reason that live vaccines continue to be carefully tested and monitored.

For their own protection, people with compromised immune systems—such as people who are taking immunosuppressive drugs, people who have cancer or people living with HIV—are usually not given live vaccines. The vaccines for yellow fever, measles, rubella, and mumps are all produced from live, attenuated organisms.

Toxoids

A toxoid is an inactivated toxin, the harmful substance produced by a microbe. Many of the microbes that infect people are not themselves harmful. It is the powerful toxins they produce that can cause illness. For example, the bacterium that causes tetanus is found everywhere in nature, and in an environment with plenty of oxygen, it is harmless. If that same organism is put into an environment without oxygen, however, the organism starts to change and produce tetanus toxin, a substance far more potent than the well-known poison sodium cyanide. To inactivate such powerful toxins, vaccine manufacturers treat them with materials known to completely cripple any disease-causing ability. Formalin, a solution of formaldehyde and sterile water, is most often used to inactivate toxins and produce toxoids. Toxoids are used to immunize people against tetanus and diphtheria.

New and Second-Generation Vaccines

Scientists are using new technologies to improve traditional vaccines. These new second-generation vaccines, as well as vaccines for diseases that had not been preventable very long ago, are made using powerful techniques such as recombinant genetic engineering (also called recombinant DNA technology).

Conjugate Vaccines

The bacteria that cause some diseases, such as pneumococcal pneumonia and certain types of meningitis, have special outer coats. These coats disguise antigens so that the immature immune systems of infants and younger children are unable to recognize these harmful bacteria. In a conjugate vaccine, proteins or toxins from a second type of organism, one that an immature immune system can recognize, are linked to the outer coats of the disease-causing bacteria. This enables a young immune system to respond and defend against the disease agent.

Currently, conjugate vaccines are available to protect against a type of bacterial meningitis caused by Haemophilus influenzae type b (Hib). Meningitis, an inflammation of the fluid-filled membranes that protect the brain and spinal cord, can be fatal, or it can cause severe, life-long disabilities such as deafness and mental retardation. Since Hib vaccines have been in widespread use in the United States, Hib meningitis has nearly disappeared among babies and young children.

Subunit Vaccines

Sometimes vaccines developed from antigenic fragments are able to evoke an immune response, often with fewer side effects than might be caused by a vaccine made from the whole organism. Subunit vaccines can be made by taking apart the actual microbe, or they can be made in the laboratory using genetic engineering techniques. Today, subunit vaccines are used to protect against pneumonia caused by Streptococcus pneumoniae and against a type of meningitis.

A recombinant subunit vaccine for hepatitis B virus infection is now licensed for use in the United States. The recombinant vaccine is made by inserting a tiny portion of the hepatitis B virus' genetic material into common baker's yeast. This process induces the yeast to produce an antigen, which is then purified. The purified antigen, when combined with an adjuvant, a substance that stimulates the immune system, results in a safe and very effective vaccine.

Recombinant Vector Vaccines

A vaccine vector, or carrier, is a weakened virus or bacterium into which harmless genetic material from another disease-causing organism can be inserted.

The vaccinia virus, the virus that causes cowpox, is now used to make recombinant vector vaccines. In the submicroscopic world of viruses, vaccinia is relatively large and has ample room to accept additional genetic fragments. A vaccinia virus with several genes from the human immunodeficiency virus (HIV) is currently being tested as a vaccine for acquired immune deficiency syndrome (AIDS). In addition, a close relative of vaccinia, canarypox virus, engineered with harmless fragments of HIV, is being tested in human volunteers as a vaccine for AIDS.

Similarly, scientists are testing a weakened bacterium—salmonella—to carry portions of such microbes as the hepatitis B virus. Currently no recombinant vector vaccines are licensed for general use in the United States.